We have recently described agonist induced Alpha 2-adrenoreceptor desensitization and affinity reduction in intact normal human platelets occurring at physiological concentrations of catecholamines. These studies indicate that circulating catecholamines continuously modulate platelet Alpha 2-adrenoreceptor agonist affinity and sensitivity. In contrast, our preliminary studies indicate that essential hypertensives show little or no change in platelet Alpha 2-adrenoreceptor agonist affinity after physiological stimuli and a delay in agonist-induced desensitization in vitro. The purpose of this grant is to define further the defect in Alpha 2-adrenoreceptor regulation in hypertension. In addition, since essential hypertension is associated with abnormal cellular distribution of sodium and Alpha 2-adrenoreceptor agonist affinity is profoundly affected by sodium concentration, we plan to test whether the defect in receptor regulation is associated with abnormal sodium homeostasis. Hypertensive and normotensive subjects will have blood drawn before and after physiological stimuli which alter platelet Alpha 2-adrenoreceptor agonist affinity in normals. Aggregatory responsiveness, Alpha 2-adrenoreceptor binding characteristics, and plasma catecholamines will be determined. The effect of sodium concentration on receptor binding with intact and broken cell preparations and on agonist-induced desensitization will be determined in vitro. In addition, manipulation of sodium intake will assess in vivo effects of sodium on platelet Alpha 2-adrenoreceptor sensitivity and affinity regulation, on intraplatelet sodium and calcium concentration, and on the presence of a plasma factor which may interact with these measures. These investigations will elucidate whether the defect in Alpha 2-adrenoreceptor regulation in hypertension is due to abnormal guanine nucleotide regulatory protein function, altered sodium homeostasis, and/or a plasma factor(s). The in vitro sodium concentration studies will distinguish between a sodium "site," a membrane-mediated sodium concentration effect, or a plasma factor(s) as a mechanism for platelet Alpha 2-adrenoreceptor regulation in normotensives and hypertensives. These studies will yield further insight into the molecular mechanisms of altered receptor affinity and regulation in hypertension.